Reaction stereospecificities

Preference for the Hofmann product olefin (i.e., the olefin with the least number of alkyl substituents and, therefore, the least stable thermodynamically) in reactions where more than one olefin may be formed (i.e., secondary and tertiary esters) was noted by DePuy and King in their early review of ester elimination reac-tions . This preference is apparent from the data of Scheer et al. (Table 3). The observed reaction path ratios (Column 2) may be compared with the simple reaction path degeneracy ratios. Column 3, i.e., statistical ratio = ratio of the number of reactive j -H atoms for each path) and with the ratios of the estimated 

Reactant Observed ratio Statistical ratio A-factor ratio 

The transjcis ratios of the olefin products of some secondary ester eliminations are shown in Table 4. There is a consistant and very similar preference 

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By a sequence of thermal and photochemical steps in the course of a simple sulfolene reaction, stereospecific isomerizations are possible429-431 (equation 71). On the other... 

Reaction of yohimbine (74) with cyanogen bromide in ethanol-chloroform afforded an isomeric mixture of (3/ )- and (3S)-ethoxy-3,4-secocyanamide derivative (562 and 563, respectively) (277, 278). It was found that the relative amounts of 562 and 563 depend on the molar ratio of ethanol to the substrate applied during the reaction. Stereospecific ring closures of 562 and 563 with hot acetic acid yielded yohimbine and pseudoyohimbine (88), respectively. 

Rose n> has distinguished between substrate specificity (which may not seem stereospecific) and reaction stereospecificity (which is always present in enzyme reactions) in a thought-provoking essay, in which he also describes the usefulness of stereospecificity generally in studying enzyme mechanisms. He has done this so much better than I could, that I will not try to add to this subject. He has also pointed out how stereo-specificity may be useful in the study of evolution. This is a subject I would like to amplify. The less we know, the more we say. Nevertheless,... 

A classic prototype of these reactions is the conversion of oxiranes into thiiranes by thiocyanate ion (Scheme 29 CHEC 5.06.4.3). Inversion at both ring carbons makes the reaction stereospecific with respect to the E Z relation of the substituents on the oxirane carbons. 

The carbonylation of both cis- and trans-2-butene in methanol in the presence of a palladium catalyst and copper (II) has demonstrated the stereochemistry of this oxymetallation of simple monoolefins (19). In the initial stages of the reaction, stereospecific trans methoxypallada-tion is observed, yielding exclusively the threo- and erythro-/3-methoxy esters, respectively (Table I). In the later stages of the reaction ds-trans isomerization of both butenes becomes increasingly important such that trans methoxypalladation to the cis-trans mixtures yield both erythro and threo products. The rate of methoxypalladation of ds-2-butene is approximately three times faster than that of the trans isomer. 

However, as the diene is made a better donor, and the dienophile a better acceptor, or vice versa, the energetic advantage of the concerted path over the stepwise seems to increase10). That is, the amount of [2 + 2] adduct formed diminishes, and the reactions become more highly stereospecific. It is cycloadditions of electron-rich dienes to electron-deficient alkenes which constitute the classic Diels-Alder reactions — stereospecific [4 + 2] cycloadditions. 

An attempt to affect the ratio of products from [47] by inclusion of ethyl iodide led to negative results. This experiment was run with the hope that intersystem crossing of some intermediate (e.g., S, biradical, or oxacarbene) might lead to a change in the product distribution and the reaction stereospecificity. 

Nakajima, K., Yamashita, A., Akama, H., Nakatsu, T., Kato, H., Hashimoto, T., Oda, J. and Yamada, Y. (1998) Crystal structures of two tropinone reductases different reaction stereospecificities in fhe same protein fold. Proc. Natl. Acad. Sci. USA, 95, 4876-81. 

A stereochemical reaction cycle is one in which all compounds are chiral and all reactions stereospecific. Although the number of compounds equals the number of reactions in a cycle, the number of chiromers may either be equal to or exceed the number of reactions by one. The term chiromer denotes any member of a set of optically pure compounds related to one another by their inclusion in the same stereochemical reaction cycle. Each enantiomer of one chiral compound may be included as a separate chiromer in a stereochemical reaction cycle. Inclusion of two sets of enantiomers provides reducible cycles that are separable into two simpler reaction cycles. 

Simmons-Smith reaction. Stereospecific synthesis of cyclopropanes by treatment of olefins with methylene iodide and zinc-copper couple. 

About 25 years ago, it was suggested that reaction stereospecificity was determined by reaction thermodynamics. Examination of the stereochemical outcomes of about 130NAD(P)-linked dehydrogenases led to the generalisation that if the equilibrium constant, defined by eqn. (6.3), is greater than 0.1 nM, B-side specificity is shown, whereas if it is less than 1 pM, A-side specificity results, and if it is in the 10 pM region, either specificity can be observed. 

Intersystem crossing from the excited singlet state of simple alkenes is inefficient. Triplet state cycloadditions, therefore, are usually achievable via triplet sensitization rather than direct irradiation.701 702 Such a process often involves exciplexes, formed between electron-poor and electron-rich alkenes,703 or 1,4-biradical intermediates (Scheme 6.45).704 Thus the tendency to achieve loose geometries in such species then favours a nonconcerted (stepwise) pathway, in which rotation about the central C—C bond occurs, eventually leading to loss of reaction stereospecifity. In general, the cycloaddition... 

The results summarized in the table were obtained without our trying to optimize reaction conditions for maximum stereospecificity. Generally, the reactions were begun at —75° to — 80°C. After all reactants were combined, the reaction mixture was held at that temperature for 30 minutes, then allowed to warm to room temperature. This procedure was followed mainly to study the effect of ketone structure on the optical yield of the carbinol product. Although the effect of temperature on reaction stereospecificity was not studied in detail, comparison of the results of runs 6 and 9 suggest that lower temperatures should give... 

R" is varied from H to CH3 to n-C4H9. From these limited results it seems that the greater the difference in size between R and R", the greater will be the stereospecificity. However, other variables—such as the structure of the asymmetric chelating agent—also have an important influence on reaction stereospecificity. This variable is under study. 

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